Different effects of class Ic and III antiarrhythmic drugs on vagotonic atrial fibrillation in the canine heart.
Effects of class Ic drug pilsicainide and class III drug MS-551 were determined in the canine model of atrial fibrillation (AF) induced under vagal stimulation. Pilsicainide injected intravenously at a dose of 1.0 mg/kg over 3 min terminated AF in six of six dogs. After pilsicainide injection, the effective refractory period (ERP) of the right atrium (RA) increased (104 +/- 22 to 122 +/- 31 ms; p < 0.05), and intraatrial conduction time (CT) increased (24%; p < 0.05) in the RA during vagal stimulation. Wavelength index (WLI; ERP/CT), an estimate of the wavelength for reentry, was decreased slightly but significantly (-2%; p < 0.05) in the RA after pilsicainide. MS-551 injected intravenously at a dose of 0.5 mg/kg over a 3-min period terminated AF in three of eight dogs. An additional dose of 0.5 mg/kg of MS-551 terminated AF in three of the remaining five dogs. After MS-551 injection, ERP increased (100 +/- 30 to 143 +/- 28 ms; p < 0.05), but CT remained unchanged in the RA, and therefore WLI was increased significantly (48%; p < 0.01). Immediately before termination of AF with test drugs, mean AF intervals (FF intervals) increased, whereas the standard deviation of FF intervals did not change significantly. In conclusion, both pilsicainide and MS-551 effectively terminated vagotonic AF after an increase in FF intervals. However, changes in WLI were different between the two test drugs. Vagotonic AF could, therefore, be terminated either by prolongation of ERP or suppression of conduction with antiarrhythmic drugs.
Hayashi
H
H
The Second Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Sugitani, Japan.
Fujiki
A
A
Tani
M
M
Usui
M
M
Inoue
H
H
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001281:Atrial Fibrillation / Q000188:drug therapy*; D016275:Atrial Function / Q000187:drug effects*; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D008012:Lidocaine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D011744:Pyrimidinones / Q000494:pharmacology; D014630:Vagus Nerve / Q000187:drug effects* / Q000502:physiology
D000889:Anti-Arrhythmia Agents; D011744:Pyrimidinones; C076259:nifekalant; D008012:Lidocaine; C042288:pilsicainide